A Chiral Vanadium(V) Complex-catalyzed Enantioselective Oxidative Homo- and Hetero-coupling of Hydroxycarbazoles

概要

Axially chiral homo- and hetero-coupled hydroxycarbazoles attract attention of many researchers owing to their potential use as a precursor of chiral ligands, pharmaceuticals, etc. However, a few reports address the enantioselective processes because of their high reactivity resulting in lack of regioselectivity and/or over-oxidation reactions. In chapter 2, the first enantioselective oxidative homo-coupling of 4-hydroxycarbazoles is described. 1 Under air atmosphere, dinuclear vanadium catalyst (Ra,S,S)-1 promoted the oxidative coupling of 4-hydroxycarbazoles 2 to give the dimeric products 3 selectively coupled at C3 position in excellent yield with up to 90% ee without the formation of any byproducts. The high racemization barriers of coupling products 3 calculated by DFT indicated the potential usefulness of the biaryl skeletons as C2-symmetric chiral ligands for asymmetric catalysis. In chapter 3, the catalytic enantioselective oxidative hetero-coupling of 3-hydroxycarbazoles 4 with 2-naphthol derivative 5 was investigated. 2 In the case of hetero-coupling of hydroxycarbazoles with other aromatic compounds, the homo-coupling of the each starting material should be avoided. When hetero-coupling of 1:1 ratio of 4 and 5 was examined using a newly developed chiral mononuclear vanadium(V) complex (Ra,S)-6 as a catalyst, hetero-coupling products 7 was obtained in up to 98% yield with 90% ee without any byproducts. The reaction took place under mild conditions and exhibited satisfactory functional group tolerance. The hetero-coupling of hydroxycarbazole derivatives 4 with various arenols provided axially chiral biarenols with high chemo-, regio-, and enantioselectivities. Aerobic oxidative hetero-coupling of 4 with β-ketoesters was also proceeded with high chemo- and stereo-selectivities under slightly modified reaction conditions (chapter 4).